GB2569463A - Human lymphoid tissue-on-chip - Google Patents

Human lymphoid tissue-on-chip Download PDF

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Publication number
GB2569463A
GB2569463A GB1902181.5A GB201902181A GB2569463A GB 2569463 A GB2569463 A GB 2569463A GB 201902181 A GB201902181 A GB 201902181A GB 2569463 A GB2569463 A GB 2569463A
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United Kingdom
Prior art keywords
human
lymphoid tissue
chip
blood
tissue
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Withdrawn
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GB1902181.5A
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GB201902181D0 (en
Inventor
Goyal Girija
E Ingber Donald
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Harvard College
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Harvard College
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Priority to GB2205718.6A priority Critical patent/GB2602935B/en
Publication of GB201902181D0 publication Critical patent/GB201902181D0/en
Publication of GB2569463A publication Critical patent/GB2569463A/en
Withdrawn legal-status Critical Current

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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/14Blood; Artificial blood
    • A61K35/17Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/28Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • A61P37/04Immunostimulants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M21/00Bioreactors or fermenters specially adapted for specific uses
    • C12M21/08Bioreactors or fermenters specially adapted for specific uses for producing artificial tissue or for ex-vivo cultivation of tissue
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00Constructional details, e.g. recesses, hinges
    • C12M23/02Form or structure of the vessel
    • C12M23/16Microfluidic devices; Capillary tubes
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/0018Culture media for cell or tissue culture
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06Animal cells or tissues; Human cells or tissues
    • C12N5/0602Vertebrate cells
    • C12N5/0634Cells from the blood or the immune system
    • C12N5/0635B lymphocytes
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06Animal cells or tissues; Human cells or tissues
    • C12N5/0602Vertebrate cells
    • C12N5/0634Cells from the blood or the immune system
    • C12N5/0636T lymphocytes
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06Animal cells or tissues; Human cells or tissues
    • C12N5/0602Vertebrate cells
    • C12N5/0634Cells from the blood or the immune system
    • C12N5/0645Macrophages, e.g. Kuepfer cells in the liver; Monocytes
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06Animal cells or tissues; Human cells or tissues
    • C12N5/0602Vertebrate cells
    • C12N5/0634Cells from the blood or the immune system
    • C12N5/0651Lymph nodes
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06Animal cells or tissues; Human cells or tissues
    • C12N5/0602Vertebrate cells
    • C12N5/069Vascular Endothelial cells
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06Animal cells or tissues; Human cells or tissues
    • C12N5/0602Vertebrate cells
    • C12N5/0693Tumour cells; Cancer cells
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5011Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing antineoplastic activity
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0861Configuration of multiple channels and/or chambers in a single devices
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2531/00Microcarriers
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2533/00Supports or coatings for cell culture, characterised by material
    • C12N2533/50Proteins
    • C12N2533/52Fibronectin; Laminin
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    • C12N2533/00Supports or coatings for cell culture, characterised by material
    • C12N2533/50Proteins
    • C12N2533/54Collagen; Gelatin
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2533/00Supports or coatings for cell culture, characterised by material
    • C12N2533/90Substrates of biological origin, e.g. extracellular matrix, decellularised tissue

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • Immunology (AREA)
  • Biotechnology (AREA)
  • Wood Science & Technology (AREA)
  • Genetics & Genomics (AREA)
  • General Health & Medical Sciences (AREA)
  • Cell Biology (AREA)
  • Hematology (AREA)
  • Biochemistry (AREA)
  • Microbiology (AREA)
  • General Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Developmental Biology & Embryology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Epidemiology (AREA)
  • Virology (AREA)
  • Sustainable Development (AREA)
  • Molecular Biology (AREA)
  • Dispersion Chemistry (AREA)
  • Clinical Laboratory Science (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Urology & Nephrology (AREA)
  • Analytical Chemistry (AREA)
  • Diabetes (AREA)
  • General Physics & Mathematics (AREA)
  • Vascular Medicine (AREA)
  • Tropical Medicine & Parasitology (AREA)

Abstract

An organ-on-a-chip microfluidic device is disclosed that mimics a human lymph node and/or human lymphoid tissue. The device can include cells from human blood and lymphatic tissue, include an extracellular matrix for the development of immune system components, and provide for the perfusion of fluids and solids resembling blood and lymphatic fluid within micrometer sized channels.

Description

5th Floor Lincoln House, 300 High Holborn, London, WC1V7JH, United Kingdom (54) Title of the Invention: Human lymphoid tissue-on-chip
Abstract Title: Human lymphoid tissue-on-chip (57) An organ-on-a-chip microfluidic device is disclosed that mimics a human lymph node and/or human lymphoid tissue. The device can include cells from human blood and lymphatic tissue, include an extracellular matrix for the development of immune system components, and provide for the perfusion of fluids and solids resembling blood and lymphatic fluid within micrometer sized channels.

Claims (1)

  1. An organ-on-a-chip microfluidic device is disclosed that mimics a human lymph node and/or human lymphoid tissue. The device can include cells from human blood and lymphatic tissue, include an extracellular matrix for the development of immune system components, and provide for the perfusion of fluids and solids resembling blood and lymphatic fluid within micrometer sized channels.
GB1902181.5A 2016-07-18 2017-07-18 Human lymphoid tissue-on-chip Withdrawn GB2569463A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
GB2205718.6A GB2602935B (en) 2016-07-18 2017-07-18 Human lymphoid tissue-on-chip

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201662363579P 2016-07-18 2016-07-18
US201662398646P 2016-09-23 2016-09-23
PCT/US2017/042657 WO2018017605A1 (en) 2016-07-18 2017-07-18 Human lymphoid tissue-on-chip

Publications (2)

Publication Number Publication Date
GB201902181D0 GB201902181D0 (en) 2019-04-03
GB2569463A true GB2569463A (en) 2019-06-19

Family

ID=60996001

Family Applications (2)

Application Number Title Priority Date Filing Date
GB2205718.6A Active GB2602935B (en) 2016-07-18 2017-07-18 Human lymphoid tissue-on-chip
GB1902181.5A Withdrawn GB2569463A (en) 2016-07-18 2017-07-18 Human lymphoid tissue-on-chip

Family Applications Before (1)

Application Number Title Priority Date Filing Date
GB2205718.6A Active GB2602935B (en) 2016-07-18 2017-07-18 Human lymphoid tissue-on-chip

Country Status (7)

Country Link
US (3) US11406975B2 (en)
EP (1) EP3484491B1 (en)
AU (1) AU2017298298B2 (en)
CA (1) CA3031439A1 (en)
GB (2) GB2602935B (en)
SG (1) SG11201900422TA (en)
WO (1) WO2018017605A1 (en)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11478798B2 (en) 2017-10-02 2022-10-25 Khalifa University of Science and Technology Microfluidic device for generating an in vitro lymph node
US20210054324A1 (en) * 2018-04-05 2021-02-25 University Of Virginia Patent Foundation 3d spatially patterned lymph node on a microfluidic device
US20210062131A1 (en) * 2018-04-11 2021-03-04 Georgia Tech Research Corporation In Vitro, Multi-Niche, Bone Marrow-on-a-Chip
WO2020075938A1 (en) * 2018-10-08 2020-04-16 주식회사 에드믹바이오 Three-dimensional in vitro liver model including porous dual flow channel and bile duct system, and method for producing same
KR102158016B1 (en) * 2018-10-08 2020-09-21 주식회사 에드믹바이오 3D Liver In Vitro Model Having Biliary System and Method for Preparing the Same
EP3666883A1 (en) * 2018-12-12 2020-06-17 Zhongke Xinray (Suzhou) Biological Technology Co., Ltd. Method and apparatus for screening compounds that have preventive and therapeutic activities against endothelial glycocalyx-related diseases
CN109569344B (en) * 2018-12-17 2021-01-08 浙江大学 Method for preparing suspended micro-droplets by using micro-fluidic device

Citations (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050079556A1 (en) * 2001-04-05 2005-04-14 Douglas Nixon Methods of detecting specific cell lysis
WO2005104755A2 (en) * 2004-04-28 2005-11-10 Vaxdesign Corporation Artificial immune system: methods for making and use
US20070155009A1 (en) * 2005-11-16 2007-07-05 University Of North Carolina At Chapel Hill Extracellular matrix components for expansion or differentiation of hepatic progenitors
US7807415B2 (en) * 2005-08-23 2010-10-05 Iq Therapeutics Bv Methods of producing stable B-lymphocytes
US20120052517A1 (en) * 2004-04-28 2012-03-01 Virginia Commonwealth University Methods for testing an immune response using cultures of t cells, b cells and dendritic cells
US20120149021A1 (en) * 2009-01-15 2012-06-14 The Charles Stark Draper Laboratory, Inc. Device for Filtration of Fluids Therethrough and Accompanying Method
US20120178097A1 (en) * 2010-05-28 2012-07-12 California Institute Of Technology Methods and design of membrane filters
US20140186414A1 (en) * 2011-06-02 2014-07-03 Children's Medical Center Corporation Methods and uses for ex vivo tissue culture systems
US20140342445A1 (en) * 2011-12-09 2014-11-20 President And Fellows Of Harvard College Organ chips and uses thereof
US20150203579A1 (en) * 2014-01-23 2015-07-23 Regeneron Pharmaceuticals, Inc. Human Antibodies to PD-1
US20150260711A1 (en) * 2002-09-27 2015-09-17 The General Hospital Corporation Microfluidic Device For Cell Separation And Uses Thereof
US20160046896A1 (en) * 2008-07-16 2016-02-18 Children's Medical Center Corporation Organ mimic device with microchannels and methods of use and manufacturing thereof
US20160091489A1 (en) * 2013-06-03 2016-03-31 University Of Florida Research Foundation, Incorporated Devices and methods for isolating cells

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EP1479760A1 (en) 2003-05-19 2004-11-24 ProBioGen AG Artificial immune organ
US20070141552A1 (en) 2004-04-28 2007-06-21 Warren William L Automatable artificial immune system (AIS)
US7855074B2 (en) 2004-04-28 2010-12-21 Vaxdesign Corp. Artificial immune system: methods for making and use

Patent Citations (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050079556A1 (en) * 2001-04-05 2005-04-14 Douglas Nixon Methods of detecting specific cell lysis
US20150260711A1 (en) * 2002-09-27 2015-09-17 The General Hospital Corporation Microfluidic Device For Cell Separation And Uses Thereof
WO2005104755A2 (en) * 2004-04-28 2005-11-10 Vaxdesign Corporation Artificial immune system: methods for making and use
US20120052517A1 (en) * 2004-04-28 2012-03-01 Virginia Commonwealth University Methods for testing an immune response using cultures of t cells, b cells and dendritic cells
US7807415B2 (en) * 2005-08-23 2010-10-05 Iq Therapeutics Bv Methods of producing stable B-lymphocytes
US20070155009A1 (en) * 2005-11-16 2007-07-05 University Of North Carolina At Chapel Hill Extracellular matrix components for expansion or differentiation of hepatic progenitors
US20160046896A1 (en) * 2008-07-16 2016-02-18 Children's Medical Center Corporation Organ mimic device with microchannels and methods of use and manufacturing thereof
US20120149021A1 (en) * 2009-01-15 2012-06-14 The Charles Stark Draper Laboratory, Inc. Device for Filtration of Fluids Therethrough and Accompanying Method
US20120178097A1 (en) * 2010-05-28 2012-07-12 California Institute Of Technology Methods and design of membrane filters
US20140186414A1 (en) * 2011-06-02 2014-07-03 Children's Medical Center Corporation Methods and uses for ex vivo tissue culture systems
US20140342445A1 (en) * 2011-12-09 2014-11-20 President And Fellows Of Harvard College Organ chips and uses thereof
US20160091489A1 (en) * 2013-06-03 2016-03-31 University Of Florida Research Foundation, Incorporated Devices and methods for isolating cells
US20150203579A1 (en) * 2014-01-23 2015-07-23 Regeneron Pharmaceuticals, Inc. Human Antibodies to PD-1

Also Published As

Publication number Publication date
AU2017298298A1 (en) 2019-02-21
US20220250055A1 (en) 2022-08-11
GB2602935B (en) 2022-10-12
AU2017298298B2 (en) 2024-03-07
CA3031439A1 (en) 2018-01-25
US11865536B2 (en) 2024-01-09
EP3484491A4 (en) 2020-02-19
US20230356216A1 (en) 2023-11-09
GB202205718D0 (en) 2022-06-01
WO2018017605A1 (en) 2018-01-25
US11406975B2 (en) 2022-08-09
GB201902181D0 (en) 2019-04-03
US20190232277A1 (en) 2019-08-01
EP3484491B1 (en) 2022-09-07
EP3484491A1 (en) 2019-05-22
SG11201900422TA (en) 2019-02-27
GB2602935A (en) 2022-07-20

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